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Biomedical subjects

R G Klein

Publications and source records attributed to R G Klein.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effect of long-term inhalation of N-nitroso-dimethylamine (NDMA) and SO2/NOx in rats.

This report focusses on preliminary results of a long-term inhalation assay with N-nitroso-dimethylamine (NDMA) at low concentrations. Chronic inhalation of 1 ppm of NDMA (4 h/day, 5 days/week) was found to be toxic in rats and diminished life expectancy by about 8 months compared to the control group. Mostly tumors of the nasal region (25/36) were observed. Inhalation of 0.2 ppm of NDMA lead to a high tumor yield in rats (20/36). At a concentration of 0.04 ppm (= 0.12 mg/m3 in air) 3 tumors of the nasal region have been found until now. In addition, a combined inhalation study of other air pollutants SO2 or NOx together with NDMA at the 0.2 ppm level is being performed. Tumors of the nasal region have been observed in the groups with SO2 + NDMA and NOx + NDMA as well as with NDMA alone. Differences in tumor response of the groups treated with NDMA alone or in combination with SO2/NOx cannot be assessed yet. The additional treatment with the air pollutants SO2 or NOx has not affected the body weight gain or any other observable parameters of the life quality of the rats.

Administration, Inhalation↗
PubMed1989

Use of imipramine in children with intractable asthma and psychiatric disorders: a warning.

Imipramine is an established treatment for anxiety in adults. Some evidence also exists that it may be beneficial in children. Because of the frequent co-occurrence of anxiety and affective symptomatology in asthmatic children, a pilot study was undertaken to obtain clinical observations on the effects of imipramine on symptoms of asthma as well as those of separation anxiety and depression in children suffering from intractable asthma. The pilot trial was terminated because of medical complications after 6 patients participated.

Adolescent↗
PubMed1988

Hyperactive boys almost grown up. II. Status of subjects without a mental disorder.

In a previous article we reported the rate of DSM-III diagnoses among 101 male adolescents (aged 16 to 23 years) in whom hyperactivity had been diagnosed between ages 6 and 12 years compared with 100 controls. This report examines the rates of dysfunction among the 52 probands and 80 control adolescents who did not receive a DSM-III diagnosis at follow-up. Contrary to expectations, there were few areas (primarily involving school adjustment) in which the formerly hyperactive children were found to be at a disadvantage and numerous areas (occupational adjustment, temperament, alcohol abuse, antisocial activities, etc) in which the groups were indistinguishable. The results are explained in accordance with a bimodal distribution of dysfunction in hyperactive children grown up. Indirectly, this model supports the construct validity of the DSM-III diagnoses attention deficit disorder with hyperactivity, substance use disorder, and antisocial personality disorder. Post hoc analyses suggest that behavior problems resulting from drug use in early adolescence have graver consequences for previously hyperactive children than normal subjects.

Achievement↗
PubMed1988

Methylphenidate and growth in hyperactive children. A controlled withdrawal study.

The effect of stimulants on growth has been controversial. Among hyperactive children receiving long-term methylphenidate hydrochloride treatment, we examined the effects of methylphenidate withdrawal on the growth of hyperactive children randomly assigned to be taken off, or remain on, the medication regimen over two consecutive summers. After one summer, no group difference in height was found, but weight was higher in the group that had been taken off methylphenidate therapy. In contrast, two summers of being off methylphenidate treatment had a significant positive effect on height but not on weight. The results document a linkage between exposure to methylphenidate and reduction in growth velocity. However, they do not address whether the medication has long-term effects on height.

Adolescent↗
PubMed1988

Hyperactive boys almost grown up. III. Methylphenidate effects on ultimate height.

The height of young adults who were treated with methylphenidate hydrochloride in childhood because of hyperactivity (average daily dose, 45 mg; duration of treatment, six months to five years) was studied. There was no significant difference in height between the treated patients (n = 61) and controls (n = 99); both groups were at the national US norm in stature. The findings indicated that methylphenidate therapy does not compromise final height, even when it has an adverse impact on children's growth rate during the active treatment phase. A compensatory growth rate, or growth rebound, appears to occur following discontinuation of stimulant therapy.

Attention Deficit Disorder with Hyperactivity↗
PubMed1988

Cognitive training in academically deficient ADDH boys receiving stimulant medication.

This study evaluated the effectiveness of a 16-week intensive cognitive training program in stimulant-treated, academically deficient ADDH boys. Cognitive training focused exclusively on academic skills and tasks, and included attack strategy training as well as self-monitoring and self-reinforcement of problem-solving behaviors and response accuracy. Control groups included remedial tutoring plus medication, and medication alone. Despite the scope of the program, the results provided no support for the notion that academically based cognitive training ameliorates the performance and achievement of academically deficient ADDH youngsters. Further, this intervention did not enhance self-esteem or attributional perceptions of academic functioning. There was poor agreement between teacher ratings of academic competence and test score changes. The lack of concordance between measures, and the scarcity of academically deficient ADDH children are discussed.

Achievement↗
PubMed1988

Various short-term assays and two long-term studies with the plasticizer di(2-ethylhexyl)phthalate in the Syrian golden hamster.

The plasticizer di(2-ethylhexyl)phthalate (DEHP) and its main metabolite monethylhexylphthalate (MEHP) were investigated in several short-term in vitro assays, including mutagenicity in Salmonella typhimurium TA102, a strain sensitive to mutations arising as a cause of oxidative DNA damage. Also DNA amplification in SV40-transformed Chinese hamster cells and DNA damage in rat and hamster hepatocytes were investigated. The two compounds were not genotoxic in any of the test systems. Furthermore, DEHP was investigated in two long-term bioassays with Syrian golden hamsters using both i.p. (max. total dose 54 g/kg) and inhalative (7-10 mg/kg) application. In both experiments an additional group of animals received a combination treatment of DEHP with N-nitrosodimethylamine (NDMA). These studies were included in order to elucidate whether the observed influence of DEHP on the microsomal enzyme activity (Seth, 1982) may effect the carcinogenic activity of NDMA. There was no significant increase in tumor incidence after application of only DEHP via both routes. However, the occurrence of liver malignancies was significantly (P less than 0.001) reduced after the combination treatment in the inhalation study.

Air Pollutants↗
PubMed1988

Effects of SO2 or NOx on toxic and genotoxic properties of chemical carcinogens. I. In vitro studies.

This paper describes in vitro studies on the effects of environmental pollutants (SO2/NOx) in biological systems. Basic physical, chemical and biochemical parameters were analyzed to establish the rate of SO2/NOx absorption by the culture medium. It was shown that the pH remains constant for 24 h of exposure to gas concentrations up to 50 p.p.m. The concentration of ions resulting from absorption of each pollutant in the liquid phase is dependent on their concentration in the gas phase and on exposure time. Short exposure times and high gas dosages resulted in similar doses in the medium as long exposure periods and low gas dosages. The activities of a human serum standard (alkaline phosphatase, ALP; aspartate amino transferase, AST; alanine amino transferase, ALT; gamma-glutamyltransferase, gamma-GT; lactate dehydrogenase, LDH) were determined after gaseous exposure to SO2 and NOx. The results revealed a distinct decrease in the activity of LDH after 1, 3 and 5 h exposure to 200 p.p.m. SO2. The effects of the pollutants were assayed in vitro using fetal hamster lung cells (FHLC), rat hepatocytes and the cell line CO60. For the determination of toxic effects, it was shown that the plating efficiency was a more sensitive parameter than the assay for trypan blue exclusion. Toxicity indicated as an increase of LDH leakage was not observed from FHLC in culture. Instead, a decrease of LDH was found following SO2 exposition. This decrease was similar to that observed for the human serum standard. The induction of DNA single-strand breaks was determined as a measure of genotoxic effects. SO2 application decreased the rate of DNA single-strand breaks induced by N-nitroso-acetoxymethyl-methylamine in both FHLC and in rat hepatocytes. SO2 or NOx treatment of CO60 cells for 1 h did not result in the induction of DNA amplification. HSO3- added directly to the medium as the sodium salt, however, distinctly induced the amplification of SV40 DNA. The amplification rates induced by benzo[a]pyrene or dimethylbenzanthracene were neither influenced by SO2, NOx nor HSO3-. An additive effect of HSO3- with either benzo[a]pyrene or dimethylbenzanthracene for this biological parameter was therefore not observed.

Air Pollutants↗
PubMed1988

Effects of SO2 or NOx on toxic and genotoxic properties of chemical carcinogens. II. Short term in vivo studies.

Short term in vivo studies were performed to study biological effects of the common air pollutants SO2 or NOx and their influence on the genotoxic activities of nitrosamines. Hepatocytes and lung cells were isolated from Sprague-Dawley rats which had inhaled 50 p.p.m. of SO2 or NOx for 2 weeks. After incubating the cells for 1 h, genotoxicity was determined in hepatocytes by measuring DNA single-strand breaks induced by N-nitroso-acetoxymethylmethylamine, N-nitrosodimethylamine and N-nitrosomethylbenzylamine. Parameters of toxicity (trypan blue exclusion and leakage of serum enzymes) were determined in both liver and lung cells also following 1 h incubation. The activities of aryl hydrocarbon hydroxylase (AHH), nitrosodimethylamine demethylase (NDMA-D) and glutathione-S-transferase (GST) were determined in subcellular microsomal fractions isolated from lung and liver tissues. Finally, as a measure of overall toxicity, the activities of various serum enzymes were determined in the blood serum of the rats. It was found that the induction of DNA single-strand breaks by three nitrosamines was decreased in hepatocytes from SO2-treated animals. The viability of rat hepatocytes and of rat lung cells, as determined by trypan blue exclusion, was similar in all three treatment groups immediately after isolation, as well as after 1 h incubation with DMSO or with the nitrosamines. In contrast, the leakage of enzymes was different in hepatocytes of SO2-treated rats, since lactate dehydrogenase activity was decreased. Leakage of enzymes from the lung cells did not differ from group to group, but was lower than from hepatocytes. Foreign compound metabolizing enzymes were mainly decreased in NOx-treated animals, namely AHH, NDMA-D and GST in liver and GST in the lung. For SO2-treated animals NDMA-D was increased in liver and GST was decreased in lung. Blood serum enzyme levels were not greatly different from each other, except for lactate dehydrogenase which was elevated in SO2-exposed animals.

Air Pollutants↗
PubMed1987

A new approach to the treatment of chronic low back pain.

81 patients with chronic low back pain (average duration 10 years) were randomised to two treatment groups. 40 received an empirically devised regimen of forceful spinal manipulation and injections of a dextrose-glycerine-phenol ("proliferant") solution into soft-tissue structures, as part of a programme to decrease pain and disability. The other 41 patients received parallel treatment in which the main differences were less extensive initial local anaesthesia and manipulation, and substitution of saline for proliferant. Neither patients nor assessors knew which treatment had been given. When assessed by disability scores the experimental group had greater improvement than the control group at one (p less than 0.001), three (p less than 0.004), and six (p less than 0.001) months from the end of treatment; at six months an improvement of more than 50% was recorded in 35 of the experimental group versus 16 of the control group and the numbers free from disability were 15 and 4, respectively (p less than 0.003). Visual analogue pain scores and pain diagrams likewise showed significant advantages for the experimental regimen.

Adult↗
PubMed1987

Exhalation of N-nitrosoethylvinylamine after application of N-nitrosodiethylamine to Sprague-Dawley rats.

Our method of endotracheal intubation makes it possible to collect exhaled air directly from the respiratory tract, thus eliminating the possibility of artefact formation and decomposition of metabolites. N-Nitrosodiethylamine (NDEA) has been postulated as a precursor of N-nitrosoethylvinylamine (NEVA), however, NEVA has not been detected as a metabolite of NDEA. Following endotracheal intubation and intravenous application of 550 micrograms NDEA to Sprague-Dawley rats, appreciable amounts of NEVA and unaltered NDEA were found in exhaled air. Further confirmation that NEVA is a metabolite of NDEA was obtained when, after eliminating oxidative decomposition of the nitrosamine with disulfiram in an enzyme inhibition assay, pretreated rats exhaled only traces of NEVA. Such findings could be informative with respect to the organotropism of nitrosamine carcinogenesis.

Animals↗
PubMed1984

Urinary excretion of N-nitrosodimethylamine in rats after Thalamonal narcosis.

Urinary excretion of N-nitrosodimethylamine (NDMA) in Sprague--Dawley rats was investigated after oral administration and inhalation of NDMA and concomitant narcosis by Thalamonal and diethyl ether. While ether anesthesia induced a 4-fold increase in the excretion rate, there was a drastic reduction (about 20-fold) in the amount of NDMA excreted after narcosis by Thalamonal.

Anesthetics↗
PubMed1984

Quantitative measurement of the exhalation rate of volatile N-nitrosamines in inhalation experiments with anaesthetized Sprague-Dawley rats.

Volatile N-nitrosamines have been detected in the human environment--in work places, such as the rubber, leather and chemical industries, in tobacco smoke and also inside new cars. In order to make risk assessments on the basis of inhalation experiments with animals at dose levels relevant to the human situation, it is important to know the actual absorption rate in the respiratory tract. In this study, 63 female Sprague-Dawley rats were exposed to four nitrosamines (N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine and N-nitrosomorpholine) in air. Respiratory parameters were monitored by pneumotachography. After 10 min of inhalation, the exhaled air was collected for 10 min in steps of 2 min intervals and analysed for its content of nitrosamines with a Thermal Energy Analyzer. Inhalation and exhalation were maintained by endotracheal intubation under narcosis with Thalamonal. The influence of this anaesthetic on the urinary excretion of N-nitrosodimethylamine after gavage and inhalation was tested: in comparison with unanaesthetized animals and with a group under ether narcosis, the excretion of the nitrosamine by the Thalamonal-anaesthetized animals was drastically reduced (factor of 20 to 60). Independent of the concentration of inhaled nitrosamine, ranging from 1-450 micrograms/L in air, the relative amounts of exhaled substance 10 min after inhalation were 0.9% N-nitrosodimethylamine, 0.4% N-nitrosodiethylamine, 6% N-nitrosopyrrolidine and 5% N-nitrosomorpholine. Extrapolation of these data back to the first exhalation (i.e., following the last inhalation) revealed that a remarkable amount of substance may be exhaled (up to 30% N-nitrosodimethylamine).

Air Pollutants↗
PubMed1983

Carcinogenicity of N-nitroso-acetoxymethyl-methylamine (acetoxymethyl-methylnitrosamine) after inhalation in rats.

Inhalation of nitroso-acetoxymethyl-methylamine (NAMMA) at a mean concentration of 0.5 ppm (= 2.6 mg/m3), 5 h/day, 5 days/week for 7 weeks proved to be highly toxic and carcinogenic in male Sprague-Dawley rats. The first tumour (a carcinoma of the lung) developed after a 14-day period of carcinogen application. The nasal region and the trachea were found to be the main target organs for the local carcinogenic activity.

Animals↗
PubMed1982

Calculations and measurements on the volatility of N-nitrosamines and their aqueous solutions.

The vapour pressures of 30 N-nitrosamines between 0 and 40 degrees C are calculated by means of well-known and experimentally proven formulae. The saturation concentration of the nitrosamines in air is presented as mmHg, ppm and mg/m3. For N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and N-nitrosopyrrolidine (NPYR) the calculated values are compared with actual measurements in the same temperature range and are found to coincide very closely. Furthermore the partial pressures of NDMA, NDEA and NPYR over an aqueous solution were experimentally determined and are tabulated in mmHg and mg/m3, for practical purposes. The calculations have been programmed in BASIC on a scientific computer, however, commercial programmable pocket calculators would also have been sufficient.

Mathematics↗